This research proposal represents a critical investigation in (1) the immunologic tolerance to sperm, and (2) the mechanisms of tissue injury in experimental allergic orchitis (EAO), a prototype of sperm immunity and of autoimmune disease. Whether immunologic tolerance to sperm exists is determined at the level of the whole animal, and of antigen reactive T and B-lymphocytes. Mechanisms of immunologic tolerance to be analyzed include: (1) clonal deletion of T or B-lymphocytes, (2) suppressor T-lymphocytes, and (3) sequestered sperm antigens. The blood-testis barrier as a means to prevent immune reaction between antibody or T-lymphocytes and sperm antigen is evaluated in an ultrastructural tracer study. The significance of T-lymphocytes and/or humoral antibody in the pathogenesis of EAO is analyzed (1) in the whole animal (in vivo) involving quantitation and tissue localization of, and passive transfer of EAO, with different immune reactants; and (2) at the cellular level, (in vitro) by studying the mechanisms of sperm-cytotoxicity by lymphocytes, macrophages or their products. Aspermatogenic antigens, isolated from sperm by detergents, chromatographic and electrophoretic techniques, are used in some of the immunopathologic studies. Their localization on sperm is determined by immunofluorescence and immunoelectron microscopy. BIBLIOGRAPHIC REFERENCES: Tung, K.S.K. Human Sperm Antigens and Antisperm Antibodies. I. Studies on Vasectomy Patients. Clin. Exp. Immunol. 20: 93-104, 1975. Tung, K.S.K. Studies on Human Sperm Acrosomal Antigens. Fed. Proc. 35: 1684, 1976.